Acetophenone → 1-Phenylethanol, (S)-

Temperature

-78 °C

(S)-1-phenylethanol was synthesized as shown in FIG. 7. Thiourea (12 mg, 0.025 mmol), which was obtained as shown in Example 1, and 4 Å molecular sieve, which was freshly dried by flame under vacuum for 30 min and cooled under argon, 250 mg, were added to an oven-dried vial and flushed with argon three times. Toluene (0.7 mL) was added to the mixture, followed by acetophenone (30 mg, 0.25 mmol). The mixture was cooled to −78° C. and a solution of catecholborane (1.0 M in Toluene, 0.4 mL, 0.4 mmol) was added slowly along the side of the vial. The resulting reaction mixture was put into a−46° C.˜−48° C. bath. After stirring for 24 hours at −46° C.˜-48° C., MeOH (1 mL) was added followed by 3 N NaOH (1 mL). The mixture was gradually warmed to room temperature and stirred for another 1 hour at room temperature, and then extracted with ether (10 mL×3), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel using Hexanes/EtOAc (6:1) as eluent to give (S)-1-phenylethanol as colorless oil (27 mg, 88% yield); 98% ee, HPLC analysis (Chiralcel OD, 250 mm×4.6 mm, 2% iPrOH/Hexane, 1.0 mL/min, 254 nm; tr(major)=19.2 min, tr(minor)=15.0 min); [α]20D=−51.7 (c 1.09, CHCl3, lit. (Sokeirik 2007) (R)-1-phenylethanol, 96% ee, [α]D=+42.92 (c 1.04, CHCl3)); 1H NMR (CDCl3, 300 MHz) δ=7.38-7.23 (m, 5H), 4.87 (q, J=6.3 Hz, 1H), 2.03 (br s, 1H), 1.90 (d, J=6.3 Hz, 3H); 13C NMR (CDCl3, 75 MHz) δ=145.9, 128.6 (2C), 127.6, 125.5 (2C), 70.5, 25.3.

1. customwas freshly dried
2. temperatureby flame under vacuum for 30 min
3. temperaturecooled under argon
4. addition250 mg, were added to an oven-dried vial and
5. customflushed with argon three times
6. additionToluene (0.7 mL) was added to the mixture
7. customThe resulting reaction mixture
8. custom46° C.˜−48° C. bath
9. temperatureThe mixture was gradually warmed to room temperature
10. stirringstirred for another 1 hour at room temperature
11. extractionextracted with ether (10 mL×3)
12. dry with materialdried over Na2SO4
13. concentrationconcentrated in vacuo
14. customThe residue was purified by flash column chromatography on silica gel

ORD record

ord-64f48275c5d54054aba2845459a79e23

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08334405B2